Disorders of food intake and energy homeostasis commonly accompany acute and chronic disease and are thought to result from proinflammatory cytokine signaling in the brain. This thesis investigates the role of the central melanocortin system in mediating these responses. Interleukin‑1β directly activates proopiomelanocortin neurons while suppressing agouti‑related protein secretion, linking inflammatory signals to anorexia and increased energy expenditure. In models of acute inflammation, chronic disease, and congestive heart failure, blockade of melanocortin signaling attenuated cachexia. These findings identify the central melanocortin system as a key mediator of cytokine‑induced metabolic dysregulation and a potential therapeutic target.
